Children <2 years old: facial and extensor surfaces
Children >2 or adults: flexor surfaces
Minor features include white dermatographism, delayed blanch response, pityriasis alba
Differential Diagnosis
Background
Usually presents <5 years old in 90% of patients
70% of children with AD have spontaneous remission before adolescence
In adults with new onset dermatitis, especially without a history of childhood eczema, asthma or allergic rhinitis, other diseases need to be considered (especially malignancy)
AD affects 2-15% of adults
~1/3rd of children with AD develop asthma, 50% develop AR, and 1/3rd with moderate-severe AD may have a food allergy
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Congenital disorders
Comel-Netherton syndrome - rare autosomal recessive SPINK5 mutation resulting in generalized erythrodermic eczematous dermatitis with flaking/exfoliation at birth or within first weeks of birth, sparse fragile hair that is bamboo-like on microscopy (trichorrhexis invaginata) by 6 months of age, failure to thrive, atopic predisposition (particularly food allergy), and pathognomonic ichthyosis linearis circumflexa after 2 years old
Diagnosis with microscopic examination of hair (bamboo stalk appearance), absent LEKTI staining on immunohistology, SPINK5 gene mutation screening
Hartnup syndrome - autosomal recessive mutation of an amino acid transporter (SLC6A19) causing lack of amino acid uptake from gut and kidneys with resultant amino acid deficiency (particularly tryptophan). May present with amino aciduria, episodic pellagra-like rash, and cerebellar ataxia.
Chronic dermatoses
Seborrheic dermatitis
Contact dermatitis (irritant or allergic) - may occur to drugs or other compounds in topical medications
Nummular eczema
Lichen simplex chronicus - not a primary process, the patient senses pruritus in an area of skin (with or without underlying pathology) and scratches/rubs repetitively causing trauma to the point of lichenification (thickening of the skin with variable scaling). May be caused by AD.
Pityriasis rubra pilaris
Psoriasiform dermatitis - most often with raised red plaques with silvery scales
Asteototic eczema - xerosis leading to pruritus, lichen simplex chronicus
Pityriasis rosea
Keratosis pilaris - papular rash “chicken skin” on face and outer aspects of the upper arms and thighs
Perioral dermatitis - small red papules around mouth > nose > eyes, exacerbated with chronic inhaled/topical steroid use, often worsens with steroids
Treatment options include metronidazole gel +/- erythromycin PO, TCI, doxycycline if >8 years old, and may take 3-6 weeks to clear
Infections and infestations
Scabies - more acute onset and, in contrast to AD, are localized in the axillae, groin and genital area with sparing of the face (>1 year old), intensely pruritic, often more family members are affected
Scaling papules on penis is scabies until proven otherwise
HIV-associated dermatitis
Infective dermatitis with HTLV-1 - occurs in Caribbean/Japanese origin, appears with Staph/Strep superinfection resistant to treatment; evaluate with HTLV-1 antibodies, PCR
Malignancy
Cutaneous T cell lymphoma (mycosis fungoides/Sezary syndrome) - epidermal malignancy of CD4+ T cells, often requires multiple and/or serial biopsy for diagnosis; most often misdiagnosed as chronic contact dermatitis, AD, or psoriasis
Langerhans cell histiocytosis
Gluconoma/glucogonoma (islet cell tumor)
Letterer-Siwe disease - infants, young children with seborrheic rash, lymphadenopathy, hepatosplenomegaly, diagnosis via biopsy
Immunodeficiencies
Wiskott-Aldrich syndrome - male; infections, petechiae, epistaxis, bloody diarrhea or history of bleeding
Diagnosis supported by thrombocytopenia with low mean platelet volume, WASP gene mutation
SCID, especially Omenn syndrome - recurrent or persistent chest infection, diarrhea, candidiasis, failure to thrive, erythroderma
Diagnosis supported by ALC <2.8 109/L in infants <3 mo, lymphocyte subsets, gene mutation screening
Zinc deficiency (acrodermatitis enteropathica) - infants with periorifacial (around mouth/anus, relative sparing of upper lip known as the U sign) and acral (extremities) dermatitis (crusted plaques with a heaped up border), alopecia, failure to thrive
Diagnosis by plasma zinc concentration, SLC39A4 gene mutation screening; low alkaline phosphatase may be low
Pyridoxine (vitamin B6) and niacin deficiency
Multiple carboxylase deficiency
Phenylketonuria
Kwashiorkor - "flaking paint" dermatitis and edema caused by diet deficient in protein but not calories, often due to unnecessarily restrictive food allergy diets in the US
Other
Dermatitis herpetiformis- may present atypically, with erythema, urticarial plaques, or papules with severe pruritus, burning/stinging, sometimes preceding the eruption by 8-12 hours (simulating scabies)
Usually occurs 20-40 yo, but children with recalcitrant eczema, pruritic impetigo and papular urticaria should be suspected of having DH
Biopsy demonstrates neutrophilic microabscesses in dermal papillae and granular IgA
Histamine intolerance - reported that a subset of adult patients with AD improve on histamine-free diet, worsen with histamine challenge
50-80% have elevated total IgE level and IgE sensitization to foods/environmental allergens, about 20-50% do not
Foods - about a third of infants and young children with AD will show clinically relevant reactivity to a common food allergen
Reaction patterns:
Immediate, non-eczematous IgE-mediated reactions, with some children developing a transient morbilliform rash 6-10 h after the initial immediate reaction (disappearing within a few hours) and considered to be a “late- phase” IgE-mediated response
Isolated eczematous delayed-type reactions, occur 6-48 hours after ingestion with flares of eczema on common AD sites, suggestive for a non IgE-mediated pattern
A combination of immediate-type reaction followed by an eczematous delayed-type reaction has been described in ~40% of children with positive OFC
NIAID guideline: test children <5 yo with moderate-severe AD for milk, egg, peanut, wheat, soy if AD is refractory to optimal treatment or if there is a recurrent history of immediate exacerbation after ingestion of a specific food
In older children and adults, Birch pollen-related foods have been described as potential triggers of AD (even when cooked)
Aeroallergens - AD may flare with topical contact with environmental allergens
Elimination diet x 4 weeks, directed by allergy testing (as described in algorithm below) vs. empiric elimination of egg and milk, as some patients may have eczema that flares with foods despite negative testing
Total IgE level - often >1000 IU/mL, but noted to be as high as 10,000-100,000 IU/mL
Evaluate infection
Bacterial culture for MRSA - consider skin and nasal cultures from child and caretaker
Fungal culture, KOH prep - consider if rash scaly or if there are nail changes
Malassezia sympodialis fungal infection is a particular problem in young adults with refractory head and neck eczema and can be diagnosed clinically, with KOH prep, and/or sIgE to Malassezia
Specialized testing
Specific IgE to Malassezia sympodialis (previously termed Pityrosporum ovale), T. rubrum, C. albicans
Specific IgE to S. aureus enterotoxin A and B - may correlate with disease severity
Anti-IgE IgG level
Specific IgE to manganese superoxide dismutase - antibodies produced against fungal enzyme manganese superoxide dismutase may cross-react with a similar human enzyme found in skin, and could result in an autoimmune inflammatory response
Filaggrin genotype test - mutation in filaggrin may result in dysfunctional epidermal barrier and is implicated in pathogenesis of AD
Null mutations found in 14-56% of patients with AD, ~13% of eczema may be due to filaggrin mutations on a population scale; note that a substantial number of patients with severe AD do not have filaggrin mutations and 40% of normal individuals with filaggrin mutations have no skin disease
May also increase risk of developing food allergy, asthma, allergic rhinitis (however it is actually not expressed in the airway), and eczema herpeticum
Available tests:
IBT test looks for six prevalent mutations (R501X, 1249insG, R2447X, 2282Δ4, E2422X, S2554X)
National Jewish PCR looks for 5 most frequent mutations in European (Caucasian) populations (R501X, 2282del4, R2447X, S3247 and 3702delG)
Physical exam: hand eczema and palmar hyperlinearity are strong clinical markers of mutations
Both respiratory and skin contact with these allergens may be important in induction/exacerbation of AD
Avoid playing on grass, carpets
Laundry
New clothing should be laundered before it is worn to reduce the content of formaldehyde and other chemicals.
Residual laundry detergent in clothing may be irritating, and, although changing to a milder detergent can be helpful, using a liquid rather than a powder detergent and adding an extra rinse cycle are more beneficial.
Avoid fabric softener and dryer sheets.
Occlusive clothing should be avoided, and cotton or cotton blends should be used (avoid wool, synthetics)
Silk and silver-impregnated clothing appear to offer some tangible benefit with almost no risk
Swimming is usually well tolerated; however, because swimming pools are treated with chlorine or bromine, patients should shower and use a mild cleanser immediately afterward and then apply moisturizers or occlusives.
Sunlight may be beneficial to some patients with AD, non-sensitizing sunscreens should be used to avoid sunburn (e.g. Vanicream sunscreen)
Avoid prolonged sun exposure which can cause irritating dryness, overheating, and sweating.
Skin cleansing
Use cleansers with minimal defatting activity and a neutral pH (e.g. Dove sensitive skin, Cetaphil, Vaniderm, Basis, Aveeno, Purpose, and Neutrogena)
Bathe at least daily in tub
Schneider: "Soak and seal method" bathe 1-2 times daily, soak 10-15 min in lukewarm water, submerge as much surface area as possible (cover exposed areas with wet towels), use gentle moisturizing cleansers only where needed (Olay Moisturinse, Aveeno Advanced Care Wash), then pat dry and apply topicals immediately
Fonacier: Soak for 20 min (with or without oatmeal or baking soda) then quickly clean with mild soap, or do a quick 5 min bath. Drip dry and apply occlusive emollient (like petroleum jelly) immediately.
Moisturizers and skin care
Aqua-phor, Hydrolatum (petroleum jelly with water), Vaseline (petroleum jelly), CeraVe (contains ceramides), Vanicream applied multiple times daily
Components: occlusives (e.g. petrolatum) retard evaporation but needs to be applied on damp/wet skin, humectants (e.g. glycerol) attract and hold water in the skin the skin, and emollients (e.g. lanolin) lubricate the stratum corneum
Vehicles: ointments best for lichenified skin and have less preservatives but are aesthetically undesirable, creams preferred for moist intertrigenous areas but requires preservatives that may be sensitizing and irritating, and solutions, gels, sprays are preferred for scalp but can contain alcohol and proylene glycol that burn and irritate
Ammonium lactate 5 or 12% (AmLactin, HydroLac, LacHydrin) BID, available OTC
Ceramide moisturizers
CeraVe cream 450 gram jar, available OTC
Osmotics TriCeram ointment 3.4 oz tube, available OTC
Can put on wet socks/gloves/pajamas and cover them with dry socks/gloves/pajamas
Unna (zinc oxide) boot dressings - cotton bandage dressing impregnated with Zn oxide which soothes irritation and keeps skin moist (some unna boots also contain calamine, glycerin, acacia, castor oil, and/or white petrolatum)
Keep dressing in place with socks, bandages, co-flex (etc.) and keep on overnight
Long term use may lead to skin maceration, folliculitis, and secondary infections or rarely adrenal suppression (with moderate-to-potent corticosteroids)
Schneider: For acute flare, apply BID x 7-14 days then wean to daily, every other day, to none. Duration should not be limited to 5-7 days, use "touch rule" (apply steroids to rough skin until smooth)
Face: use class VI-VII e.g. aclometasone dip. 0.05% ointment, desonide 0.05% ointment, hydrocortisone 1-2.5% ointment
Body: use class II or lower, e.g. mometasone furoate 0.1% ointment (II), triamcinolone acetonide 0.1% ointment (III), mometasone furoate 0.1% cream (IV), hydrocortisone valerate 0.2% ointment (IV)
Scalp: use mid-low potency oil, lotion, foam, or gel
For preventative treatment of previously involved but now normal-appearing skin: apply steroid used for treatment 2 consecutive nights weekly
Clinical pearl - for AD patients with immediate rebound after stopping steroid or if steroid has to be used every day, the steroid potency is probably too low (provided that all other aspects of eczema care are maximized)
Oral corticosteroids - effective but associated with rebound flare-up, requires tapering, reserved for crisis management
Especially useful in areas prone to atrophy: eyelid, perioral, genital, axilla, inguinal
Protopic (tacrolimus) 0.1% ointment has the strength of a mid-potency topical corticosteroid and should be considered first-line therapy for facial eczema where treatment with corticosteroids is limited because of safety concerns
Protopic is approved for use in Europe as twice-weekly maintenance/proactive therapy to areas typically with AD in patients as young as 2 years of age for up to 12 months
Adverse reactions
A local burning sensation is the only common adverse event, with a reduction of this sensation within 3 days of initiating therapy
FDA black box warning regarding increased risk of malignancy discourages prolonged use (see below)
TCIs may increase risk for topical viral infections (eczema herpeticum, molluscum) of treated skin and patients should be monitored for this complication
A small percentage of patients can experience facial flushing after an alcoholic beverage
Use with caution in children <2 years old (due to high body surface/weight ratio), and patients with abnormal epidermis (e.g. Netherton’s syndrome) because significant percutaneous absorption of TCIs could occur, which may result in systemic serum concentrations known to cause immunosuppression
Anti-pruritic strategies
Oral - most effective for sedation
Children: Hydroxyzine 2 mg/kg PO QHS
Older patients:
Doxepin - up to 1 mg/kg PO QHS
Paroxetine (Paxil) - 10 mg PO QHS
Mirtazapine - 7.5-45 mg PO QHS
Schneider: cetirizine QAM and hydroxyzine or diphenhydramine 1 mg/kg PO QHS
Topical
Pramoxine (Prax lotion, Sarna)
Ice pack PRN
Antibiotics for superinfection
Bleach baths - usually 1/4-1/2 cup of regular (unscented unconcentrated) liquid bleach per 40 gallon bathtub 3-5 times/week (for small baby bathtubs, 10 mL per gallon) = 0.005 % final concentration or ~0.5 cup of 6% bleach in a full bathtub
Unclear whether effectiveness can be explained by S. aureus reduction or astringent effect
Lio: daily when flaring, 2-3 times/week for maintenance, soak for 10 min
Burning sensation can occur with open lesions
Rinse off with clean water if there are concerns about skin irritation
Malassezia infection - consider itraconazole 100 mg PO QD x 2 months then 100 mg Qweek (Lio)
Anti-Staph - MSSA usually more important than MRSA; refractory cases suggest MRSA
Oral
Cephalexin 50 mg/kg/day div PO TID x 7-14 days (adults 1-4 g/day div BID-QID), dicloxacillin if able to swallow tablets
MRSA: Clindamycin, TMP-SMX, doxycycline/minocycline; 7-10 days often sufficient
Topical - for localized impetiginized lesions and treatment of nasal MRSA carriage
Bactroban (mupirocin 2%) topical ointment, TID up to 12 days for impetigo, 15, 22, 30g
Bactroban nasal (mupirocin calcium 2%) ointment indicated for treatment of nasal MRSA carriers, 0.5 g intranasal BID x 5 days, supplied as 10-pack of 1 g tubes
Altabax (retapamulin 1%) topical ointment, BID x 5 days for impetigo, 5, 10, 15g
Antiseptic cleansers - may be used for patients with frequent bacterial infections on the whole body or critical areas only, however some concern for systemic absorption limits these antiseptics to patients with weepy-type AD, mothers with AD that have small babies, patients with elevated risk for systemic infection (e.g. catheters, chronic wounds, immunodeficiency)
Triclosan 1-2% soaps include pHisoderm, Dial liquid, Softsoap liquid hand soap
Chlorhexidine gluconate 0.5-1% include Hibiclens and Hex-A-Clens
Vitamin D deficiency may play a role in decreased antimicrobial peptide production
Other antibacterial measures:
“Spring cleaning” the patient’s bedroom, washing and replacing the linen, and wiping down surfaces and toys may help to reduce re-infection from fomites
Tubs and tubes of moisturizers and ointments may need replacing if there is a risk of bacterial contamination
Coal tar
Tar preparations - Fonacier: "Help control itching, redness and scaling when all else fails"
Coal tar bar soap, T-gel shampoo, Triton Mg 217 medicated tar ointment 3.8 oz
Compound formula with 10% liquid coal tar distillate, 5% salicylic acid, 3% lactic acid in aquaphor ointment base
Antipruritic and anti-inflammatory effects similar to class 7 steroid, should only be used in chronic lesions, can be used as monotherapy or in combination with topical steroids. Shampoo good for AD involving scalp.
Adverse effects include photosensitivity, folliculitis, odor/dark color stains clothes and decreases compliance
Immunotherapy
Some data indicate that immunotherapy can be effective for AD when it is associated with aeroallergen (particularly dust mite) sensitivity
Practice parameter 2012: patients with AD may benefit from supplementation with vitamin D, particularly if they have a documented low level or low vitamin D intake
Flohr: Initially 2.5 mg/kg/d, increase to maximum of 5 mg/kg/d in exceptional circumstances
Fonacier
Dose: 3-5 mg/kg/d for 6 weeks (children as young as 22 mo responded to 2.5 mg/kg/d), then decrease 1 mg/kg/d every 2 weeks until at 1 mg/kg/d, then increase dose interval by 1 day every 2 weeks with goal of discontinuing after 3-6 months
PeDRA (Pediatric Dermatology Research Alliance)
Dose: 5 mg/kg/day (300 mg/d max), maintain x 3 mo then taper (max 1 year)
AD Working Group (2012): 5 mg/kg/d div BID, weaned by 1 mg/kg/d per month, discontinued completely after 6 months
Rapid 2-3 week response, most with good response (93%), but rebound in 50%, 10% with sustained remission >6 months, risk of renal toxicity requiring lab monitoring
May be most effective for AD driven by secondary bacterial skin infections rather than allergens
Limit to 1 year
Flohr: CBC/diff, CMP, BP at baseline, then q2 weeks x 2 mo then q3 mo
Fonacier: BP, CBC/diff, CMP q2 weeks x 3 mo then monthly, Cr x 3 prior to start, glucose, HgbA1C, Mg, CsA level
PeDRA: BP Qweek x 4 then Qmo; CBC, LFTs, BUN/Cr, CMP, uric acid, lipids Qmo x 3 then Q2 mo
Azathioprine
PeDRA: check patient's baseline thiopurine methyltrasferase (TPMT) activity, if normal 2.5-3.5 mg/kg/day, if intermediate, use 1 mg/kg/day. Maintain x 3 months then taper (max 2 years)
Flohr: Initially 1 mg/kg/d, increase to maximum of 3 mg/kg/d, taking account of TPMT result; TPMT <3 nmol/h/mL – contraindicated, TPMT 3-8 nmol/h/ mL – low dose 0.5-1 mg/kg/day, TPMT 8-14.5 nmol/h/mL 1-3 mg/kg/day, TPMT >14.5 nmol/h/mL consider >3 mg/kg/day if no response
Onset slow (4-8 weeks) therefore can use concurrent prednisone for 1 month
Potential adverse effects include myelotoxicity, headache, GI upset, hepatotoxicity
There are concerns about risk of lymphoma and progressive multifocal leukoencephalopathy; unclear if these would occur in patients treated for AD
Limit to 2 years
PeDRA: CBC, LFTs, BUN/Cr, at 2, 4, 8, 12 weeks then q8 weeks
Flohr:
CBC/diff, CMP, and TPMT levels at baseline, then q1 week for first month, then q3 mo
Increases in dose should be accompanied by weekly blood tests
Repeat blood count if severe throat infection or other signs of potential marrow suppression
Methotrexate
Initially 200 mg/kg once weekly increased to a maximum of 400 mg/kg once weekly, depending on response. Test dose is usually given at start of therapy, followed by blood a week later.
Folic acid is given at least once weekly in conjunction with MTX (5 mg weekly on a different day). However, folic acid regimens vary, and evidence is not conclusive as to which is most efficacious.
Onset of action is slow (4-8 weeks)
GI symptoms (nausea), LFT abnormalities, and bone marrow suppression are potential side effects, but MTX is generally well tolerated and considered safe in the long-term (based on rheumatologic experience in children and adults)
The SC route can be used if PO ineffective or nausea is severe
Lio:
Consider adding Silybum marianum (milk thistle 250 mg PO BID) to protect liver
For nausea, divide dose to BID, ginger root/snaps
CBC/diff, CMP, CXR, procollagen III (only in adults because unreliable in growing children) at baseline then q2 weeks x 1st mo and at this frequency after each dose change
Lio: baseline CBC, CMP, hepatitis panel, recheck at 1 week then q4-6 weeks
Mycophenolate mofetil
40-60 mg/kg/d (3 grams/d maximum)
Onset 1‐2 months
Can use concurrent prednisone or cyclosporine x 1 month
Limit to 2 years
CBC, CMP at 1 month then qMo
LFTs 3Mo
Interferon-gamma - may be useful as a treatment for moderate-to-severe atopic dermatitis patients who have a history of recurrent skin infections with HSV, molluscum contagiosum, or HPV
Phototherapy and photochemotherapy
Dermatology referral, helpful in 60% of refractory cases, narrow band UVB (311 nm) safe
Natural sunlight is beneficial but avoid sunburn and excessive sweating
Adverse effects include an increased risk of developing skin cancer, itch, acute burns
Lio: narrow band UVB 3 times/week can be an incredibly powerful treatment for those who are not responding adequately to aggressive topical management, and can stave off more powerful immunosuppressant medications in some
Low-mid potency steroids will not cause clinically significant adrenal suppression
Arkwright: Contrary to common belief, there is little objective evidence that long-term use of topical corticosteroids causes chronic skin atrophy, adrenal suppression, growth retardation, or reduced bone mineral density
Table of Contents
Clinical Diagnosis
Differential Diagnosis
Background
- Usually presents <5 years old in 90% of patients
- 70% of children with AD have spontaneous remission before adolescence
- In adults with new onset dermatitis, especially without a history of childhood eczema, asthma or allergic rhinitis, other diseases need to be considered (especially malignancy)
- AD affects 2-15% of adults
- ~1/3rd of children with AD develop asthma, 50% develop AR, and 1/3rd with moderate-severe AD may have a food allergy
spaceAD vs. Hyper IgE syndromes
History and Physical
Testing
Treatment
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Treatments for Recalcitrant Disease
Experimental or Unproven Treatments
Adverse Effects of Therapy
Malignancy Risks
Note:
Topical Steroids (Schneider)
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References
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Resources for Patients